Abstract

There is
increasing evidence that aging is affected by biological (circadian) clocks
- the internal mechanisms that coordinate daily changes in gene expression,
physiological functions and behavior with external day/night cycles.
Recent data suggest that disruption of the mammalian circadian clock
results in accelerated aging and increased age-related pathologies such as
cancer; however, the links between loss of daily rhythms and aging are not
understood. We sought to determine whether disruption of the circadian
clock affects lifespan and healthspan in the model organism Drosophila
melanogaster. We examined effects of a null mutation in the circadian
clock gene period (per01) on the fly healthspan by
challenging aging flies with short-term oxidative stress (24h hyperoxia)
and investigating their response in terms of mortality hazard, levels of
oxidative damage, and functional senescence. Exposure to 24h hyperoxia
during middle age significantly shortened the life expectancy in per01
but not in control flies. This homeostatic challenge also led to
significantly higher accumulation of oxidative damage in per01
flies compared to controls. In addition, aging per01
flies showed accelerated functional decline, such as lower climbing ability
and increased neuronal degeneration compared to age-matched controls.
Together, these data suggest that impaired stress defense pathways may
contribute to accelerated aging in the per mutant. In addition, we
show that the expression of per gene declines in old wild type
flies, suggesting that the circadian regulatory network becomes impaired
with age.